The proposed research involves the synthesis of insulin and insulin analogs by the step-wise method of disulfide bond formation. The synthetic route provides for the initial formation of an insulin A chain containing a preformed A6-11 disulfide loop with differential protection (Cys7-S-AcM, Cys2o-s-Tr) at the remaining cysteine residues. The B-chain derivative will be prepared from natural insulin; the Cys-B7 and B19 residues will be selectively alkylated with acetamidomethyl cation to provide the B chain with the Cys7 sulfhydryl group protected as the S- Acm derivative.